| Airborne particulate matter increases MUC5AC expression by downregulating Claudin-1 expression in human airway cells. |
| Sang-Su Kim1, Cheol Hong Kim2, Ji Wook Kim1, Hsi Chiang Kung1, Tae Woo Park1, Yu Som Shin1, Ju Deok Kim1, Siejeong Ryu1, Wang-Joon Kim3, Yung Hyun Choi4, Kyoung Seob Song3,* |
1Department of Anesthesiology and Pain Medicine, Kosin University College of Medicine,
2Department of Pediatrics, Sungkyunkwan University Samsung Changwon Hospital,
3Department of Physiology, Kosin University College of Medicine,
4Department of Biochemistry, College of Korean Medicine, Don-Eui University |
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Abstract
CLB2.0, a constituent of PM, induces secretion of multiple cytokines and chemokines that regulate airway inflammation. Specifically, IL-6 upregulated CLB2.0-induced MUC5AC and MUC1 expression. Interestingly, of the tight junction proteins examined, claudin-1 expression was inhibited by CLB2.0. While overexpression of claudin-1 decreased CLB2.0-induced MUC5AC expression, it increased expression of the anti-inflammatory mucin, MUC1. CLB2.0-induced IL-6 secretion was mediated by ROS. The ROS scavenger N-acetyl-cysteine inhibited CLB2.0-induced IL-6 secretion, thereby decreasing CLB2.0-induced MUC5AC expression, whereas CLB2.0-induced MUC1 expression was increased. CLB2.0 activated the ERK1/2 MAPK via a ROS-dependent pathway. ERK1/2 downregulated claudin-1 expression and MUC1 expression, whereas it dramatically increased CLB2.0-induced MUC5AC expression. These findings suggest that CLB2.0-induced ERK1/2 activation acts as a switch for regulating inflammatory conditions though a ROS-dependent pathway. Our data also suggest that secreted IL-6 regulates CLB2.0-induced MUC5AC and MUC1 expression via ROS-mediated downregulation of claudin-1 expression to maintain mucus homeostasis in the airway.
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| Abstract, Accepted Manuscript(in press) [Submitted on June 14, 2017, Accepted on September 5, 2017] |
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